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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3
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Publication Metadata only The risk of recurrence in endometrial cancer patients with low-volume metastasis in the sentinel lymph nodes: a retrospective multi-institutional study(MDPI, 2023) Buda, Alessandro; Paniga, Cristiana; Taskin, Salih; Mueller, Michael; Zapardiel, Ignacio; Fanfani, Francesco; Puppo, Andrea; Casarin, Jvan; Papadia, Andrea; De Ponti, Elena; Grassi, Tommaso; Mauro, Jessica; Turan, Hasan; Gungor, Mete; Ortag, Firat; Imboden, Sara; Garcia-Pineda, Virginia; Mohr, Stefan; Siegenthaler, Franziska; Perotto, Stefania; Landoni, Fabio; Ghezzi, Fabio; Scambia, Giovanni; Fruscio, Robert; Vatansever, Doğan; Taşkıran, Çağatay; School of MedicineThe surgical management of apparent early-stage endometrial cancer is still unclear. Nodal involvement is prognostic, but the role of retroperitoneal staging is still debated. Sentinel node mapping has been introduced and accepted as a valid alternative to full lymphadenectomy. Furthermore, ultrastaging provides a more accurate analysis of the excised lymph nodes by detecting a higher rate of low-volume metastasis. The aim of this study was to evaluate the impact of low-volume metastasis on recurrence-free survival in women with apparent early-stage endometrial cancer in a large retrospective multi-institutional collaboration.The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.Publication Metadata only Impact of persistent PSA after salvage radical prostatectomy: a multicenter study(Springernature, 2023) Preisser, Felix; Incesu, Reha-Baris; Rajwa, Pawel; Chlosta, Marcin; Nohe, Florian; Ahmed, Mohamed; Abreu, Andre Luis; Cacciamani, Giovanni; Ribeiro, Luis; Kretschmer, Alexander; Westhofen, Thilo; Smith, Joseph A.; Steuber, Thomas; Calleris, Giorgio; Raskin, Yannic; Gontero, Paolo; Joniau, Steven; Sanchez-Salas, Rafael; Shariat, Shahrokh F.; Gill, Inderbir; Karnes, R. Jeffrey; Cathcart, Paul; Van Der Poel, Henk; Marra, Giancarlo; Tilki, Derya; School of Medicine; Koç University HospitalBackground and Objective: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. Material and Methods: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value >= 0.1 ng/ml, at first PSA-measurement after salvage RP. Results: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). Conclusion: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.Publication Metadata only Characteristics of incidental prostate cancer in the United States(Springernature, 2023) Scheipner, Lukas; Incesu, Reha-Baris; Morra, Simone; Baudo, Andrea; Assad, Anis; Jannello, Letizia Maria Ippolita; Siech, Carolin; de Angelis, Mario; Barletta, Francesco; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; Briganti, Alberto; Chun, Felix K. H.; Longo, Nicola; Carmignani, Luca; De Cobelli, Ottavio; Ahyai, Sascha; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalBackground: Data regarding North-American incidental (cT1a/b) prostate cancer (PCa) patients is scarce. To address this, incidental PCa characteristics (age, PSA values at diagnosis, Gleason score [GS]), subsequent treatment and cancer-specific survival (CSS) rates were explored. Methods: Incidental PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). Descriptive statistics, annual percentage changes (EAPC), Kaplan-Meier estimates, as well as Cox regression models were used. Bootstrapping technique was used to generate 95% confidence intervals for CSS at 6 years. Results: Of all 344,031 newly diagnosed non metastatic PCa patients, 5155 harbored incidental PCa. Annual rates of incidental PCa increased from 1.9% (2004) to 2.5 % (2015; p = 0.02). PSA values at diagnosis were 0-4 ng/ml in 48% vs. 4-10 ng/ml in 31% vs. > 10 ng/ml in 21%. Of all incidental PCa patients, 64% harbored GS 6 vs. 25% GS 7 vs. 11% GS >= 8. Of all incidental PCa patients, 47% were aged < 70, 35% were between 70 and 79 and 18% were >= 80 years. Subsequently, 71% underwent no local treatment (NLT) vs. 16% radical prostatectomy (RP) vs. 14% radiotherapy (RT). Proportions of patients with NLT increased from 65 to 81% (p = 0.0001) over the study period (2004-2015). CSS at six years ranged from 58% in GS >= 8 patients with NLT to 100% in patients who harbored GS 6 and underwent either RP or RT. Conclusion: Incidental PCa in the United States is rare. Most incidental PCa patients are diagnosed in men aged less than 80 years of age. The majority of incidental PCa patients undergo NLT and enjoy excellent CSS.Publication Metadata only Prognostic significance of pathologic lymph node invasion in metastatic renal cell carcinoma in the immunotherapy era(Springer, 2023) Scheipner, Lukas; Barletta, Francesco; Garcia, Cristina Cano; Incesu, Reha-Baris; Morra, Simone; Baudo, Andrea; Assad, Anis; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; Briganti, Alberto; Chun, Felix K. H.; Longo, Nicola; Carmignani, Luca; Pichler, Martin; Ahyai, Sascha; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalBackground: This study aimed to test the prognostic significance of pathologically confirmed lymph node invasion in metastatic renal cell carcinoma (mRCC) patients in this immunotherapy era. Methods: Surgically treated mRCC patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Kaplan-Meier plots and multivariable Cox-regression models were fitted to test for differences in cancer-specific mortality (CSM) and overall mortality (OM) according to N stage (pN0 vs pN1 vs. pNx). Subgroup analyses addressing pN1 patients tested for CSM and OM differences according to postoperative systemic therapy status.Results: Overall, 3149 surgically treated mRCC patients were identified. Of these patients, 443 (14%) were labeled as pN1, 812 (26%) as pN0, and 1894 (60%) as pNx. In Kaplan-Meier analyses, the median CSM-free survival was 15 months for pN1 versus 40 months for pN0 versus 35 months for pNx (P < 0.001). In multivariable Cox regression analyses, pN1 independently predicted higher CSM (hazard ratio [HR], 1.88; P < 0.01) and OM (HR, 1.95; P < 0.01) relative to pN0. In sensitivity analyses addressing pN1 patients, postoperative systemic therapy use independently predicted lower CSM (HR, 0.73; P < 0.01) and OM (HR, 0.71; P < 0.01). Conclusion: Pathologically confirmed lymph node invasion independently predicted higher CSM and OM for surgically treated mRCC patients. For pN1 mRCC patients, use of postoperative systemic therapy was associated with lower CSM and OM. Consequently, N stage should be considered for individual patient counseling and clinical decision-making.Publication Metadata only Prognostic significance of pathological lymph node invasion in metastatic renal cell carcinoma in the immunotherapy era(Springer, 2023) Scheipner, Lukas; Barletta, Francesco; Garcia, Cristina Cano; Incesu, Reha-Baris; Morra, Simone; Baudo, Andrea; Assad, Anis; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; Briganti, Alberto; Chun, Felix K. H.; Longo, Nicola; Carmignani, Luca; Pichler, Martin; Ahyai, Sascha; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalN/APublication Metadata only Aso visual abstract: in-hospital venous thromboembolism and pulmonary embolism after major urological cancer surgery(Springer, 2023) Garcia, Cristina Cano; Tappero, Stefano; Piccinelli, Mattia Luca; Barletta, Francesco; Incesu, Reha-Baris; Morra, Simone; Scheipner, Lukas; Baudo, Andrea; Tian, Zhe; Hoeh, Benedikt; Chierigo, Francesco; Sorce, Gabriele; Saad, Fred; Shariat, Shahrokh F.; Carmignani, Luca; Ahyai, Sascha; Longo, Nicola; Briganti, Alberto; De Cobell, Ottavio; Dell'Oglio, Paolo; Mandel, Philipp; Terrone, Carlo; Chun, Felix K. H.; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalN/APublication Metadata only In-hospital venous thromboembolism and pulmonary embolism after major urologic cancer surgery(Springer, 2023) Garcia, Cristina Cano; Tappero, Stefano; Piccinelli, Mattia Luca; Barletta, Francesco; Incesu, Reha-Baris; Morra, Simone; Scheipner, Lukas; Baudo, Andrea; Tian, Zhe; Hoeh, Benedikt; Chierigo, Francesco; Sorce, Gabriele; Saad, Fred; Shariat, Shahrokh F.; Carmignani, Luca; Ahyai, Sascha; Longo, Nicola; Briganti, Alberto; De Cobell, Ottavio; Dell'Oglio, Paolo; Mandel, Philipp; Terrone, Carlo; Chun, Felix K. H.; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalBackground: This study aimed to test for temporal trends of in-hospital venous thromboembolism (VTE) and pulmonary embolism (PE) after major urologic cancer surgery (MUCS). Methods: In the Nationwide Inpatient Sample (NIS) database (2010-2019), this study identified non-metastatic radical cystectomy (RC), radical prostatectomy (RP), radical nephrectomy (RN), and partial nephrectomy (PN) patients. Temporal trends of VTE and PE and multivariable logistic regression analyses (MLR) addressing VTE or PE, and mortality with VTE or PE were performed. Results: Of 196,915 patients, 1180 (1.0%) exhibited VTE and 583 (0.3%) exhibited PE. The VTE rates increased from 0.6 to 0.7% (estimated annual percentage change [EAPC] + 4.0%; p = 0.01). Conversely, the PE rates decreased from 0.4 to 0.2% (EAPC - 4.5%; p = 0.01). No difference was observed in mortality with VTE (EAPC - 2.1%; p = 0.7) or with PE (EAPC - 1.2%; p = 0.8). In MLR relative to RP, RC (odds ratio [OR] 5.1), RN (OR 4.5), and PN (OR 3.6) were associated with higher VTE risk (all p < 0.001). Similarly in MLR relative to RP, RC (OR 4.6), RN (OR 3.3), and PN (OR 3.9) were associated with higher PE risk (all p < 0.001). In MLR, the risk of mortality was higher when VTE or PE was present in RC (VTE: OR 3.7, PE: OR 4.8; both p < 0.001) and RN (VTE: OR 5.2, PE: OR 8.3; both p < 0.001). Conclusions: RC, RN, and PN predisposes to a higher VTE and PE rates than RP. Moreover, among RC and RN patients with either VTE or PE, mortality is substantially higher than among their VTE or PE-free counterparts.Publication Metadata only Critical appraisal of leibovich 2018 and grant models for prediction of cancer-specific survival in non-metastatic chromophobe renal cell carcinoma(MDPI, 2023) Piccinelli, Mattia Luca; Morra, Simone; Tappero, Stefano; Cano Garcia, Cristina; Barletta, Francesco; Incesu, Reha-Baris; Scheipner, Lukas; Baudo, Andrea; Tian, Zhe; Luzzago, Stefano; Mistretta, Francesco Alessandro; Ferro, Matteo; Saad, Fred; Shariat, Shahrokh F. F.; Carmignani, Luca; Ahyai, Sascha; Briganti, Alberto; Chun, Felix K. H.; Terrone, Carlo; Longo, Nicola; de Cobelli, Ottavio; Musi, Gennaro; Karakiewicz, Pierre I. I.; Tilki, Derya; School of Medicine; Koç University HospitalSimple Summary :To date, guideline-recommended prognostic models predicting cancer-control outcomes in chromophobe kidney cancer patients have never been validated in a large-scale contemporary North American cohort. We addressed this knowledge gap and performed a formal validation of Leibovich 2018 and GRade, Age, Nodes and Tumor (GRANT) prognostic models with cancer-specific survival as an outcome. Moreover, we proposed a novel nomogram for the prediction of the same outcome. Within the Surveillance, Epidemiology, and End Results database (2000-2019), we identified 5522 unilateral surgically treated non-metastatic chromophobe kidney cancer (chRCC) patients. This population was randomly divided into development vs. external validation cohorts. In the development cohort, the original Leibovich 2018 and GRANT categories were applied to predict 5- and 10-year cancer-specific survival (CSS). Subsequently, a novel multivariable nomogram was developed. Accuracy, calibration and decision curve analyses (DCA) tested the Cox regression-based nomogram as well as the Leibovich 2018 and GRANT risk categories in the external validation cohort. The accuracy of the Leibovich 2018 and GRANT models was 0.65 and 0.64 at ten years, respectively. The novel prognostic nomogram had an accuracy of 0.78 at ten years. All models exhibited good calibration. In DCA, Leibovich 2018 outperformed the novel nomogram within selected ranges of threshold probabilities at ten years. Conversely, the novel nomogram outperformed Leibovich 2018 for other values of threshold probabilities. In summary, Leibovich 2018 and GRANT risk categories exhibited borderline low accuracy in predicting CSS in North American non-metastatic chRCC patients. Conversely, the novel nomogram exhibited higher accuracy. However, in DCA, all examined models exhibited limitations within specific threshold probability intervals. In consequence, all three examined models provide individual predictions that might be suboptimal and be affected by limitations determined by the natural history of chRCC, where few deaths occur within ten years from surgery. Further investigations regarding established and novel predictors of CSS and relying on large sample sizes with longer follow-up are needed to better stratify CSS in chRCC.Publication Metadata only Demographics, clinical characteristics and survival outcomes of primary urinary tract malignant melanoma patients: a population-based analysis(MDPI, 2023) Morra, Simone; Incesu, Reha-Baris; Scheipner, Lukas; Baudo, Andrea; Jannello, Letizia Maria Ippolita; de Angelis, Mario; Siech, Carolin; Goyal, Jordan A.; Tian, Zhe; Saad, Fred; Califano, Gianluigi; la Rocca, Roberto; Capece, Marco; Shariat, Shahrokh F.; Ahyai, Sascha; Carmignani, Luca; de Cobelli, Ottavio; Musi, Gennaro; Briganti, Alberto; Chun, Felix K. H.; Longo, Nicola; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalSimple Summary: Primary urinary tract malignant melanoma represents a rare malignancy. To date, analyses exclusively addressing contemporary diagnosed patients are unavailable. However, historical series reported lower survival rates of primary urinary tract malignant melanoma patients relative to their cutaneous counterparts. We aimed to describe the demographics, clinical characteristics, and survival outcomes of contemporary diagnosed primary urinary tract malignant melanoma patients, identified within a large-scale North American cohort.Abstract All primary urinary tract malignant melanoma (ureter vs. bladder vs. urethra) patients were identified from within the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020. Kaplan-Maier plots depicted the overall survival (OS) rates. Univariable and multivariable Cox regression (MCR) models were fitted to test the differences in overall mortality (OM). In the overall cohort (n = 74), the median OS was 22 months. No statistically significant or clinically meaningful differences were recorded according to sex (female vs. male; p = 0.9) and treatment of the primary (endoscopic vs. surgical; p = 0.6). Conversely, clinically meaningful but not statistically significant (p & GE; 0.05) differences were recorded according to the patient's age at diagnosis (& LE;80 vs. & GE;80 years old; p = 0.2), marital status (married 26 vs. unmarried 16 months; p = 0.2), and SEER stage (localized 31 vs. regional 14 months; p = 0.4), and the type of systemic therapy (exposed 31 vs. not exposed 20 months; p = 0.06). Finally, in univariable and MCR analyses, after adjustment for the SEER stage and type of systemic therapy, tumor origin within the bladder was associated with a three-fold higher OM (Hazard ratio: 3.00; p = 0.004), compared to tumor origin within the urethra. In conclusion, primary urinary tract malignant melanoma patients have poor survival. Specifically, tumor origin within the bladder independently predicted a higher OM, even after adjustment for the SEER stage and systemic therapy status.Publication Metadata only Oncologic outcomes of lymph node dissection at salvage radical prostatectomy(MDPI, 2023) Preisser, Felix; Incesu, Reha-Baris; Rajwa, Pawel; Chlosta, Marcin; Ahmed, Mohamed; Abreu, Andre Luis; Cacciamani, Giovanni; Ribeiro, Luis; Kretschmer, Alexander; Westhofen, Thilo; Smith, Joseph A.; Graefen, Markus; Calleris, Giorgio; Raskin, Yannic; Gontero, Paolo; Joniau, Steven; Sanchez-Salas, Rafael; Shariat, Shahrokh F.; Gill, Inderbir; Karnes, Robert Jeffrey; Cathcart, Paul; van der Poel, Henk; Marra, Giancarlo; Tilki, Derya; School of Medicine; Koç University HospitalSimple Summary: Lymph node invasion represents a poor prognostic factor after primary radical prostatectomy for prostate cancer. However, its impact on oncologic outcomes in salvage radical prostatectomy patients is unknown. Within this study we investigated the impact of lymph node invasion and dissection on the oncologic outcomes after salvage prostatectomy. Our results show that lymph node invasion represents are poor prognostic factor after salvage prostatectomy. Conversely, we recorded no benefit for lymph node dissection compared to no lymph node dissection during salvage prostatectomy. These findings underline the need for a cautious indication of lymph node dissection in salvage prostatectomy patients as well as strict postoperative monitoring of patients with lymph node invasion. Background: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown. Objective: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients. Patients and methods: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan-Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS). Results: Of 853 SRP patients, 87% (n = 727) underwent LND, and 21% (n = 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 (p < 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% (p < 0.001), and CSS rates were 94% vs. 96% vs. 82% (p = 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77, p < 0.001) and death (HR: 2.89, p < 0.001). Conclusions: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.